Recombinant Human Epidermal Growth Factor/Quatsome Nanoconjugates: A Robust Topical Delivery System for Complex Wound Healing

Abstract

A multitude of microparticles and nanoparticles is developed to improve the delivery of different small drugs and large biomolecules, which are subject to several hindering biological barriers that limit their optimal biodistribution and therapeutic effects. Here, a soft, reliable, and scalable method based on compressed CO2 is reported for obtaining nanoconjugates of recombinant human epidermal growth factor and nanovesicles called quatsomes, where the latter consists of cholesterol and cetyltrimethylammonium bromide. These nanoconjugates exhibit appropriate values of the major critical quality attributes of colloidal nanomedicines, such as controlled and narrow nanoscopic particle size distribution (which play important roles in determining their stability), drug loading, drug release, drug protection, targeting ability, and bioactivity. Also, they exhibit a dual action by 1) inbuilt antimicrobial activity preventing infections and 2) promoting regeneration of granulation tissue and re‐epithelialization with complete closure of complex wounds. Therefore, such nanoconjugates are a potential nanomedicine for the topical treatment of complex wounds, particularly diabetic foot ulcers and venous leg ulcers.

DELOS Nanovesicles-Based Hydrogels: An Advanced Formulation for Topical Use

“…In addition, these nanoconjugates are attractive skin nanocarrier candidates since being considered a well-tolerated liquid dispersion by this route. This has been confirmed by not only the human epidermis EpiSkin model but also by the outstanding results in terms of the cicatrization of the treated complex wounds for compassionate patient treatment [8,9]. Thus, considering the potential of DELOS vesicles in topical administration, here we propose, as a proof of concept, the possibility of transforming the DELOS nanovesicle liquid dispersion to a semi-solid dosage form as an improved pharmaceutical product for topical delivery.…”

“…DELOS nanovesicles were prepared by DELOS-SUSP (Depressurization of an Expanded Liquid Organic Solution-Suspension) as schematically represented in Figure S1 (Supplementary Materials) and described in refs. [8,17]. This methodology is based on first weighing the membrane components, cholesterol, and the surfactant (CTAB or CTAC) in a 1:1 molar ratio of cholesterol:surfactant and then dissolving them in ethanol.…”

“…Previous studies based on the development of novel nanoconjugates of DELOS nanovesicles integrating a recombinant human Epidermal Growth Factor (rhEGF) presented huge potentiality for epidermal regeneration. rhEGF was integrated into Quatsomes composed of cholesterol and the quaternary ammonium surfactant cetyltrimethylammonium bromide (CTAB), resulting in a feasible strategy for topical drug delivery such as complex wound treatment [8]. These nanoconjugates, in liquid dispersion, displayed proper physicochemical characteristics and higher efficacy in wound reepithelization when comparing it to the free protein on its own.…”

“…Besides their capability to act as nanocarriers for delivering small drugs and bioactive macromolecules (proteins, enzymes, RNA, etc. ), DELOS nanovesicles have been also acknowledged due to the intrinsic antimicrobial properties of their membrane composition, mainly because of the presence of ionic surfactants, like quaternary ammonium surfactants, which can help to protect skin from infections [8]. Indeed, these cationic surfactants have a broad versatility of applications: in cosmetics and pharmaceutical formulations they are used as antimicrobial preservatives, and therapeutically as topical antiseptic for skin, burns, and wounds.…”

Biocosmetics: technological advances and future outlook

“…Gomes et al 2020 (Gomes et al 2020) discuss some of these biotechnological processes and products used for developing cosmetic formulations. Some of the active ingredients resulting from biotechnological processes are kojic acid (Lajis et al 2013), hyaluronic acid (Pan et al 2015;Cheng et al 2017), resveratrol (Donnez et al 2009), human epidermal growth factors (Ferrer-Tasies et al 2021), superoxide dismutase (Carroll et al 2007), and photolyases (Marizcurrena et al 2020). Traditional biotechnology exploits the potential of microbes via fermentation, while modern biotechnology manipulates the genetic material and inserts it in a suitable host for the desired application.…”